Clinical features and signaling effects of RET D631Y variant multiple endocrine neoplasia type 2 (MEN2)

Background/Aims@#Germline mutations of the rearranged during transfection (RET) gene cause multiple endocrine neoplasia type 2 (MEN2). About 85% of RET mutations in MEN2 occur in codon Cys634. The RET D631Y mutation has recently been discovered, and we have studied its molecular expression and clinical consequences. @*Methods@#We analyzed the clinical characteristics of a total of 34 D631Y variant MEN2 individuals from seven families. We also constructed wild-type and mutant C630Y, D631Y, and C634R/W expression vectors and investigated their effects on signaling pathways and ability to correct the phenotypes of RET mutant cells. @*Results@#The median ages at diagnosis of pheochromocytoma and medullary thyroid carcinoma (MTC) were higher in patients with RET D631Y variant MEN2 than in those with the C634R/W variant (49:53.5 years vs. 33.5:27 years, respectively), and the penetration of the D631Y mutation with respect to MTC was lower than that of the C634R/W mutation (32.3% vs. 90%). The effects of the mutant vectors on phosphorylation of RET signaling molecules and focus formation were significantly different from those of wild type, but there were no significant differences between the mutants. D631Y scored significantly higher for chemotaxis and wound healing than C630Y, but lower than C634R and C634W. @*Conclusions@#We suggest that the tumorigenic potential conferred by the D631Y mutation is lower than that conferred by the C634R/W mutation, but higher than that conferred by C630Y. Thus, the risk level of the RET D631Y variant appears to be higher than that of C630Y and lower than that of C634R/W.

Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency

BACKGROUND: We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of CYP17A1. METHODS: To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes. RESULTS: Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure. CONCLUSION: Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous CYP17A1 mutations.

An Endobronchial Lipoma Treated by Bronchoscopic Excision / 대한내과학회지

A 68-year-old man presented with partial atelectasis of the right middle lobe on chest X-ray. Computed tomography of the chest revealed a hypodense mass in the middle lobe. Bronchoscopy showed a round mass obstructing the right middle lobe bronchus, and a biopsy specimen revealed only chronic inflammation. The tumor was removed using rigid bronchoscopy, and a diagnosis of endobronchial lipoma was made. An endobronchial lipoma is a very rare benign tumor that may cause parenchymal lung damage due to bronchial obstruction and subsequent pneumonia. We report this case to emphasize the role of endoscopic treatment in the management of endobronchial lipoma.

A Case of Acute Pyelonephritis Complicated with Renal Vein Thrombosis / 대한신장학회지

Acute pyelonephritis is a common disease in clinical practice. Renal vein thrombosis in acute pyelonephritis has become a rare complication at present because of the advances of antibiotics. The trend in management has shifted to non-surgical therapies, particularly systemic anticoagulation, except in highly selected group of patients. Here we report the case of a 67-year-old woman who got hospitalized for fever and chilling. Acute pyelonephritis was diagnosed by clinical manifestation and positive urine and blood cultures. Computed tomography demonstrated left pyelonephritis and ipsilateral renal vein thrombosis. She was fully recovered after treatment with antibiotics, low molecular weight heparin and warfarin for 8 weeks.

A Case of Multidrug-resistant Acinetobacter baumannii Ventriculitis Successfully Treated with Intrathecal Colistimethate / 감염과화학요법

Acinetobacter species is a non-fermentative aerobic gram-negative coccobacillus that is an important pathogen found in nosocomial infections. Recently, multi-drug resistant Acinetobacter baumannii (MDR-AB) infections have been increasing and pose a serious problem. Most such infections present as bacteremia, pneumonia, or a wound infection; however, CNS infections are very rare. We herein present a case of ventriculitis caused by MDR-AB in a 37-year old man after a neurosurgical intervention. The patient was successfully treated with intrathecal colistimethate.

A Case of Multidrug-resistant Acinetobacter baumannii Ventriculitis Successfully Treated with Intrathecal Colistimethate / 감염과화학요법

Acinetobacter species is a non-fermentative aerobic gram-negative coccobacillus that is an important pathogen found in nosocomial infections. Recently, multi-drug resistant Acinetobacter baumannii (MDR-AB) infections have been increasing and pose a serious problem. Most such infections present as bacteremia, pneumonia, or a wound infection; however, CNS infections are very rare. We herein present a case of ventriculitis caused by MDR-AB in a 37-year old man after a neurosurgical intervention. The patient was successfully treated with intrathecal colistimethate.